The primary goals of this project are: 1) the development and implementation of quantitative physical models for the demineralization and remineralization of tooth enamel; and 2) the application of these models to the design and optimization of therapies for the prevention or reversal of caries. Work proposed for the coming project period will rely heavily on physical models and the accompanying experimental techniques already developed in this project. These models will enable the approach of correlating crystallite kinetic behavior with the kinetics and morphology observed at the lesion level to be extended to encompass demineralization, remineralization, subsequent acid challenge and repetitive cycles of exposure to conditions intended to simulate the in vivo environment. Crystal growth studies in suspension systems will be extended to include the effects of carbonate on growth kinetics. Studies with block enamel will utilize a model independent data analysis technique developed in this project. This technique allows fluoride, carbonate and mineral density profiles determined at successive time intervals to be used to deduce the time history of the micro-environmental solution chemistry within the enamel as a function of both time and position. Thus the relationship between local rate of growth or dissolution and solution composition during lesion formation can be determined. These approaches have led to our proposing several alternative models for the demin/remin process: a coexistence model, in which crystal faces that are not readily remineralized coexist with those which are extensively remineralized; an overcoat model, in which growth occurs on all crystal faces, possibly entrapping relatively soluble carbonate apatite beneath a coating of fluorhydroxyapatite; and a crystal maturation model in which behavior can range from coexistence to overcoat, depending on the microenvironmental solution composition and length of exposure to remineralization conditions.